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Metabolism of T-2 toxin in farm animals and human in vitro and in chickens in vivo using ultra high-performance liquid chromatography- quadrupole/time-of-flight hybrid mass spectrometry along with online hydrogen/deuterium exchange technique

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Abstract
After being incubated with animal and human liver microsomes, metabolites of phase I and II were investigated. A comparison was performed by ultrahigh performance liquid chromatography-quadrupole/time-of-flight coupled to mass spectrometry (UHPLC-Q/TOF). Consequently, a total of four phase I metabolites and three glucuronide binding metabolites of T-2 toxin were discovered. Although a significant metabolic difference was observed among six species, HT-2 toxin was the major product in all species. In addition, the in vivo metabolism of T-2 toxin after oral administration was also investigated in chickens, In total, 18 metabolites were detected, of which 13 were novel, to our knowledge, and reported for the first time. To elucidate the structures of these metabolites, besides accurate mass data from their MS and MS2 spectra, online hydrogen/deuterium (H/D) exchange technique was also carried out. These new metabolites were regarded as 3'-hydroxy-T-2 3-sulfate, 3'-hydroxy-HT-2 3-sulfate, 4'-hydroxy-HT-2, 3',4'-dihydroxy-HT-2, 4'-carboxyl-T-2, 4'-carboxyl-HT-2, 4'-carboxyl-4'-hydroxy-T-2, and their isomers, implying that T-2 toxin was metabolized more extensively in animals than previously thought. Furthermore, 3'-hydroxy-HT-2, 4'-carboxyl-T-2, 3'-hydroxy-T-2, HT-2 toxin, and neosolaniol were identified to be the major metabolites of T-2 toxin in chickens. The present study expands existing knowledge about T-2 toxin metabolism, informing assessments of the impact T-2 toxin exposure and metabolism on health.
Keywords
TRICHOTHECENE MYCOTOXIN, BROILER-CHICKENS, DRUG-METABOLISM, HT-2 TOXIN, IDENTIFICATION, MICROSOMES, TOXICITY, PATHWAYS, RATS, DEOXYNIVALENOL, T-2 toxin, metabolism, comparative, human, animals

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Chicago
Yang, Shupeng, Marthe De Boevre, Huiyan Zhang, Karl De Ruyck, Feifei Sun, Jinzhen Zhang, Yue Jim, et al. 2017. “Metabolism of T-2 Toxin in Farm Animals and Human in Vitro and in Chickens in Vivo Using Ultra High-performance Liquid Chromatography- Quadrupole/time-of-flight Hybrid Mass Spectrometry Along with Online Hydrogen/deuterium Exchange Technique.” Journal of Agricultural and Food Chemistry 65 (33): 7217–7227.
APA
Yang, Shupeng, De Boevre, M., Zhang, H., De Ruyck, K., Sun, F., Zhang, J., Jim, Y., et al. (2017). Metabolism of T-2 toxin in farm animals and human in vitro and in chickens in vivo using ultra high-performance liquid chromatography- quadrupole/time-of-flight hybrid mass spectrometry along with online hydrogen/deuterium exchange technique. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 65(33), 7217–7227.
Vancouver
1.
Yang S, De Boevre M, Zhang H, De Ruyck K, Sun F, Zhang J, et al. Metabolism of T-2 toxin in farm animals and human in vitro and in chickens in vivo using ultra high-performance liquid chromatography- quadrupole/time-of-flight hybrid mass spectrometry along with online hydrogen/deuterium exchange technique. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY. 2017;65(33):7217–27.
MLA
Yang, Shupeng, Marthe De Boevre, Huiyan Zhang, et al. “Metabolism of T-2 Toxin in Farm Animals and Human in Vitro and in Chickens in Vivo Using Ultra High-performance Liquid Chromatography- Quadrupole/time-of-flight Hybrid Mass Spectrometry Along with Online Hydrogen/deuterium Exchange Technique.” JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 65.33 (2017): 7217–7227. Print.
@article{8546822,
  abstract     = {After being incubated with animal and human liver microsomes, metabolites of phase I and II were investigated. A comparison was performed by ultrahigh performance liquid chromatography-quadrupole/time-of-flight coupled to mass spectrometry (UHPLC-Q/TOF). Consequently, a total of four phase I metabolites and three glucuronide binding metabolites of T-2 toxin were discovered. Although a significant metabolic difference was observed among six species, HT-2 toxin was the major product in all species. In addition, the in vivo metabolism of T-2 toxin after oral administration was also investigated in chickens, In total, 18 metabolites were detected, of which 13 were novel, to our knowledge, and reported for the first time. To elucidate the structures of these metabolites, besides accurate mass data from their MS and MS2 spectra, online hydrogen/deuterium (H/D) exchange technique was also carried out. These new metabolites were regarded as 3'-hydroxy-T-2 3-sulfate, 3'-hydroxy-HT-2 3-sulfate, 4'-hydroxy-HT-2, 3',4'-dihydroxy-HT-2, 4'-carboxyl-T-2, 4'-carboxyl-HT-2, 4'-carboxyl-4'-hydroxy-T-2, and their isomers, implying that T-2 toxin was metabolized more extensively in animals than previously thought. Furthermore, 3'-hydroxy-HT-2, 4'-carboxyl-T-2, 3'-hydroxy-T-2, HT-2 toxin, and neosolaniol were identified to be the major metabolites of T-2 toxin in chickens. The present study expands existing knowledge about T-2 toxin metabolism, informing assessments of the impact T-2 toxin exposure and metabolism on health.},
  author       = {Yang, Shupeng and De Boevre, Marthe and Zhang, Huiyan and De Ruyck, Karl and Sun, Feifei and Zhang, Jinzhen and Jim, Yue and Li, Yanshen and Wang, Zhanhui and Zhang, Suxia and Zhou, Jinhui and Li, Yi and De Saeger, Sarah},
  issn         = {0021-8561},
  journal      = {JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY},
  language     = {eng},
  number       = {33},
  pages        = {7217--7227},
  title        = {Metabolism of T-2 toxin in farm animals and human in vitro and in chickens in vivo using ultra high-performance liquid chromatography- quadrupole/time-of-flight hybrid mass spectrometry along with online hydrogen/deuterium exchange technique},
  url          = {http://dx.doi.org/10.1021/acs.jafc.7b02575},
  volume       = {65},
  year         = {2017},
}

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